Biological embedding of early-life exposures and disease risk in humans: a role for DNA methylation

Eur J Clin Invest. 2015 Mar;45(3):303-32. doi: 10.1111/eci.12406.

Abstract

Background: Following wider acceptance of 'the thrifty phenotype' hypothesis and the convincing evidence that early-life exposures can influence adult health even decades after the exposure, much interest has been placed on the mechanisms through which early-life exposures become biologically embedded.

Materials and methods: In this review, we summarize the current literature regarding biological embedding of early-life experiences. To this end, we conducted a literature search to identify studies investigating early-life exposures in relation to DNA methylation changes. In addition, we summarize the challenges faced in investigations of epigenetic effects, stemming from the peculiarities of this emergent and complex field. A proper systematic review and meta-analyses were not feasible given the nature of the evidence.

Results: We identified seven studies on early-life socio-economic circumstances, 10 studies on childhood obesity and six studies on early-life nutrition all relating to DNA methylation changes that met the stipulated inclusion criteria. The pool of evidence gathered, albeit small, favours a role of epigenetics and DNA methylation in biological embedding, but replication of findings, multiple comparison corrections, publication bias and causality are concerns remaining to be addressed in future investigations.

Conclusions: Based on these results, we hypothesize that epigenetics, in particular DNA methylation, is a plausible mechanism through which early-life exposures are biologically embedded. This review describes the current status of the field and acts as a stepping stone for future, better designed investigations on how early-life exposures might become biologically embedded through epigenetic effects.

Keywords: Biological embedding; DNA methylation, epigenetics; body mass index; early-life nutrition; early-life socio-economic status.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Body Mass Index
  • Child
  • Child Nutritional Physiological Phenomena / physiology*
  • Child, Preschool
  • DNA Methylation / physiology*
  • Disease Susceptibility / etiology*
  • Environmental Exposure / adverse effects
  • Epigenesis, Genetic / physiology
  • Female
  • Humans
  • Infant
  • Life Change Events
  • Male
  • Middle Aged
  • Pediatric Obesity / complications
  • Risk Factors
  • Socioeconomic Factors
  • Young Adult